Charge density of cation determines inner versus outer shell coordination to phosphate in RNA

Nguyên, Hoàng; Thirumalai, D.

doi:10.1101/2020.03.10.986091

Cited by 6 publications

(9 citation statements)

References 60 publications

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“…RNA consists of a series of negatively charged phosphate groups in its phosphodiester backbone, but it still folds into a well-shaped compact structure overcoming the huge electrostatic repulsion. 1 The presence of positively charged metal ions, hence, is crucial not only for charge neutralization, but they also coherently dećor the ion atmosphere of RNA, in such a way, that RNA gets its optimal ambiance to fold and function. 2−9 Among different prevalent metal ions in cellular composition, magnesium is eventually unique in stabilizing the compact fold of RNA.…”

Section: ■ Introductionmentioning

confidence: 99%

Chelated Magnesium Logic Gate Regulates Riboswitch Pseudoknot Formation

et al. 2021

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Magnesium plays a critical role in the structure, dynamics, and function of RNA. The precise microscopic effect of chelated magnesium on RNA structure is yet to be explored. Magnesium is known to act through its diffuse cloud around RNA, through the outer sphere (water-mediated), inner sphere, and often chelated ion-mediated interactions. A mechanism is proposed for the role of experimentally discovered site-specific chelated magnesium ions on the conformational dynamics of SAM-I riboswitch aptamers in bacteria. This mechanism is observed with atomistic simulations performed in a physiological mixed salt environment at a high temperature. The simulations were validated with phosphorothioate interference mapping experiments that help to identify crucial inner-sphere Mg2+ sites prescribing an appropriate initial distribution of inner- and outer-sphere magnesium ions to maintain a physiological ion concentration of monovalent and divalent salts. A concerted role of two chelated magnesium ions is newly discovered since the presence of both supports the formation of the pseudoknot. This constitutes a logical AND gate. The absence of any of these magnesium ions instigates the dissociation of long-range pseudoknot interaction exposing the inner core of the RNA. A base triple is the epicenter of the magnesium chelation effect. It allosterically controls RNA pseudoknot by bolstering the direct effect of magnesium chelation in protecting the functional fold of RNA to control ON and OFF transcription switching.

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Section: ■ Introductionmentioning

confidence: 99%

Chelated Magnesium Logic Gate Regulates Riboswitch Pseudoknot Formation

et al. 2021

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“…For that, we divided RNA into two subgroups: cations around the phosphate backbone and cations around major grooves. The concentration around each group is estimated as ( 58 )cfalse(Xifalse)=gXifalse(rmaxfalse)cbulkwhere X i ≡{phosphate group, major groove} represents the two subgroups for residue i . We used O1P and O2P atoms to represent the backbone phosphate group.…”

Section: Methodsmentioning

confidence: 99%

Differences in ion-RNA binding modes due to charge density variations explain the stability of RNA in monovalent salts

2022

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The stability of RNA increases as the charge density of the alkali metal cations increases. The molecular mechanism for this phenomenon remains elusive. To fill this gap, we performed all-atom molecular dynamics pulling simulations of HIV-1 trans-activation response RNA. We first established that the free energy landscape obtained in the simulations is in excellent agreement with the single-molecule optical tweezer experiments. The origin of the stronger stability in sodium compared to potassium is found to be due to the differences in the charge density–related binding modes. The smaller hydrated sodium ion preferentially binds to the highly charged phosphates that have high surface area. In contrast, the larger potassium ions interact with the major grooves. As a result, more cations condense around phosphate groups in the case of sodium ions, leading to the reduction of electrostatic repulsion. Because the proposed mechanism is generic, we predict that the same conclusions are valid for divalent alkaline earth metal cations.

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“…For that, we divided RNA into two subgroups: cations around the phosphate backbone, and cations around major grooves. The concentration around each group is estimated as, 66 where, X i ≡{Phosphate group, Major groove}represents the two subgroups for residue i . We used O1P and O2P atoms to represents the backbone phosphate group.…”

Section: Methodsmentioning

confidence: 99%

Differences in Ion-RNA binding modes due to charge density variations explain the stability of RNA in monovalent salts

Henning-Knechtel¹,

Thirumalai

Kırmızıaltın³

2022

Preprint

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The stability of RNA increases as the charge density of the alkali metal cations increases. The molecular mechanism for the stability does not exist. To fill this gap, we performed all-atom molecular dynamics (MD) pulling simulations to dissect the microscopic origin of this phenomenon. We first established that the free energy landscape obtained in the simulations is in excellent agreement with the single-molecule optical tweezer experiments. The origin of the stronger stability in Na+ compared to K+ is found to be due to the differences in the charge-density related binding modes. The smaller hydrated Na+ ion preferentially binds to the highly charged phosphates. In contrast, the larger K+ ions interact with the major grooves. As a result, the electrostatic repulsion between the phosphate groups is reduced more effectively by Na+ ions. Because the proposed mechanism is generic, we predict that the same conclusions are valid for divalent alkaline earth metal cations.

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Charge density of cation determines inner versus outer shell coordination to phosphate in RNA

Cited by 6 publications

References 60 publications

Chelated Magnesium Logic Gate Regulates Riboswitch Pseudoknot Formation

Chelated Magnesium Logic Gate Regulates Riboswitch Pseudoknot Formation

Differences in ion-RNA binding modes due to charge density variations explain the stability of RNA in monovalent salts

Differences in Ion-RNA binding modes due to charge density variations explain the stability of RNA in monovalent salts

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